Endothelial Progenitors: A Consensus Statement on Nomenclature

Abstract

Endothelial progenitor cell (EPC) nomenclature remains ambiguous and there is a general lack of concordance in the stem cell field with many distinct cell sub-types continually grouped under the term “EPC”. It would be highly advantageous to agree standards to confirm an endothelial progenitor phenotype and this should include detailed immunophenotyping, potency assays, and clear separation from haematopoietic angiogenic cells which are not endothelial progenitors. In this review, we seek to discourage the indiscriminate use of ‘EPCs’, and instead propose precise terminology based on defining cellular phenotype and function. Endothelial colony forming cells (ECFCs) and myeloid angiogenic cells (MACs) are examples of two distinct and well-defined cell types that have been considered ‘EPCs’ because they both promote vascular repair, albeit by completely different mechanisms of action. It is acknowledged that scientific nomenclature should be a dynamic process driven by technological and conceptual advances; ergo the ongoing ‘EPC’ nomenclature ought not to be permanent and should become more precise in the light of strong scientific evidence. This is especially important as these cells become recognised for their role in vascular repair in health and disease; and, in some cases, progress towards use in cell therapy.

MicroRNA‐129‐1‐3p regulates cyclic stretch–induced endothelial progenitor cell differentiation by targeting Runx2

“…The Student t test was used for two-sample comparisons and one-way ANOVA was performed to detect whether a significant difference existed between three or five groups. 27 Our results demonstrated that EPCs are negative for CD45 expression (Supporting Information Figure S1). shape by days 8 to 10.…”

Consensus guidelines for the use and interpretation of angiogenesis assays

“…In 1997, Asa-hara and colleagues [189] reported on the identification of circulating progenitor cells for the endothelial lineage. Subsequent studies have clarified that those putative “endothelial progenitor cells” (EPC) did not possess the capacity to undergo a stable lineage switch to the endothelium, but were comprised of numerous hematopoietic cells that can serve paracrine pro-angiogenic functions to promote vascular repair and replacement but are incapable of integrating as a bona fide EC in the injured vasculature [190]. In fact, these pro-angiogenic cells can upregulate “endothelial cell” markers and thus give the impression they were becoming EC at sites of injury, but failed to persist as functional vasculature long term.…”

“…A study by the Mayr lab later showed that these are in fact mononuclear cells and that the “endothelial” surface markers were acquired by a process of membrane fusion with platelet microparticles [191]. Only endothelial colony-forming cells (ECFC), also called late outgrowth or blood outgrowth EC (BOEC), are direct EC precursors that form vessels in vivo [190]. This paragraph will briefly discuss available evidence for and remaining controversies regarding the evaluation of endothelial stem and progenitor cells in mouse and man.…”

“…If the EPC in question cannot directly give rise to cells of the endothelial lineage at a clonal level (in vitro or in vivo) or function as a bona fide EC in vivo, then the term EPC should not be applied to those cells [190]. The work of Patel et al [201] has shown that endothelial progenitors can be identified by applying stringent criteria.…”

Isolating and expanding endothelial progenitor cells from peripheral blood on peptide‐functionalized polystyrene surfaces

“…Since the first description of putative EPCs, these progenitors have been shown to directly contribute to various vascular regeneration mechanisms due to their availability in the circulating blood and their high proliferative capacity (Asahara et al, 1997(Asahara et al, , 1999. Different cell populations grouped under the term "EPC" can be distinguished based on phenotypic and functional attributes (Medina et al, 2017). For example, two distinct cell populations expressing endothelial cell markers can be obtained by culturing peripheral blood mononuclear cells (PBMCs) in different conditions: myeloid angiogenic cells and endothelial colony-forming cells (ECFCs).…”